Therapeutic effect and molecular mechanism of Salvia Miltiorrhiza on rats with acute brain injury after carbon monoxide poisoning based on the strategy of internet pharmacology

• Published in: Environmental toxicology 2022-03, Vol.37 (3), p.413-434
• Main Authors: Li, Ze‐Kun, Li, Chun‐Hua, Yue, Ao‐Chun, Song, Hui‐Ping, Liu, Xu‐Han, Zhou, Xu‐Dong, Bi, Ming‐Jun, Han, Wei, Li, Qin
• Format: Article
• Language: English
• Subjects: acute brain injury; Angiogenesis; Animals; Apoptosis; Brain; Brain Injuries - drug therapy; Brain injury; Carbon; Carbon monoxide; Carbon monoxide poisoning; Carbon Monoxide Poisoning - drug therapy; Edema; Endothelial Cells; Head injuries; Hyperbaric; Hyperbaric oxygen; Inhalation; Injury analysis; Internet; internet pharmacology; Male; MAP kinase; MAPK/ERK1/2 signaling pathway; Network analysis; Pathogenesis; Pharmacology; Poisoning; Proteins; Rats; Rats, Sprague-Dawley; Respiration; Salvia miltiorrhiza; Signal transduction; Signaling; Tanshinones; Therapeutic targets; Traumatic brain injury; Vascular endothelial growth factor
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23408

The pathogenesis of brain injury caused by carbon monoxide poisoning (COP) is very complex, and there is no exact and reliable treatment in clinic. In the present study, we screened the therapeutic target and related signal pathway of Salvia Miltiorrhiza for acute COP brain injury, and clarified the pharmacological mechanism of multicomponent, multitarget, and multisignal pathway in Salvia Miltiorrhiza by network pharmacology. To further verify the therapeutic effect of Salvia Miltiorrhiza on acute brain injury based on the results of network analysis, a total of 216 male healthy Sprague Dawley rats were collected in the present study and randomly assigned to a normal control group, a COP group and a Tanshinone IIA sulfonate treatment group (72 rats in each group). The rat model of acute severe COP was established by the secondary inhalation in a hyperbaric oxygen chamber. We found that Salvia Miltiorrhiza had multiple active components, and played a role in treating acute brain injury induced by COP through multiple targets and multiple pathways, among them, MAPK/ERK1/2 signaling pathway was one of the most important. COP can start apoptosis process, activate the MAPK/ERK1/2 signaling pathway, and promote the expression of VEGF‐A protein and the formation of brain edema. Tanshinone IIA can effectively inhibit apoptosis, up‐regulate the expressions of VEGF‐A, P‐MEK1/2 and P‐ERK1/2 proteins, thereby protect endothelial cells, promote angiogenesis and microcirculation, and finally alleviate brain edema.